The immune response in autoimmune conditions, such as, rheumatoid arthritis (RA), is dominated by the production of autoantibodies against ‘self’-antigens. Many of those rheumatoid arthritis-specific autoantibodies are generated against citrullinated antigens, such as, citrulline residues on, for example, fibrin, filaggrin and vimentin.
Citrullination is the post-translational conversion of arginine to citrulline by the enzyme peptidylarginine deiminase that is up-regulated under inflammatory conditions. This process evokes an autoreactivity towards the citrullinated residues, leading to the development of rheumatoid arthritis in susceptible individuals, among other factors.
Citrullinated peptides are typically used as a biomarker diagnostic tool in rheumatoid arthritis patients for serologic detection of anti-citrullinated protein antibodies. However, anti-citrullinated protein antibodies can be detected even before the onset of the disease symptoms and are associated with a more aggressive disease course (Meyer O. et al. Ann Rheum Dis 2003; 62:120-6).
US 2012/0225820 to Hill et al. disclose citrullinated antigenic peptides associated with rheumatoid arthritis.
Delwig et al. (Arthrithis & Rheumatism, 62(1): 143-149, 2010) disclose the proliferative response of peripheral blood mononuclear cells (PBMCs) to citrullinated aggrecan peptide in RA patients and not in healthy controls. Delwig et at further disclose the lack of response to noncitrullinated analog peptide and suggests the use of citrullinated aggrecan peptide as a biomarker to RA.
Feitsma et al. (Arthrithis & Rheumatism, 62(1): 117-125, 2010) disclose citrullinated vimentin peptides naturally processed and recognized by peptide-specific T cells of RA patients.
Catalan et al. (Reumatol Int., 32: 1819-1825, 2012) disclose CD4+ T-cells response to citrullinated vimentin in RA patients.
Shin et al. (Immune Network, 13(4):116-122, 2013) discloses CD4+ T-cells response to citrullinated fibrinogen in RA patients.
There remains an unmet need for therapeutic approaches for the treatment of autoimmune diseases, such as, rheumatoid arthritis which do not involve broad immune suppression.